314 results on '"Feuerstein B"'
Search Results
102. Effect of polyamine depletion on chromatin structure in U-87 MG human brain tumour cells
- Author
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Basu, H S, primary, Sturkenboom, M C J M, additional, Delcros, J G, additional, Csokan, P P, additional, Szollosi, J, additional, Feuerstein, B G, additional, and Marton, L J, additional
- Published
- 1992
- Full Text
- View/download PDF
103. Effects of variation in the structure of spermine on the association with DNA and the induction of DNA conformational changes
- Author
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Basu, H S, primary, Schwietert, H C A, additional, Feuerstein, B G, additional, and Marton, L J, additional
- Published
- 1990
- Full Text
- View/download PDF
104. Atomic structure dependence of nonsequential double ionization of He, Ne and Ar in strong laser pulses.
- Author
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De Jesus, V. L B., Feuerstein, B., Zrost, K., Fischer, D., Rudenko, A., Afaneh, F., Schröter, C. D., Moshammer, R., and Ullrich, J.
- Published
- 2004
105. Subshell Resolved Measurements of Single Electron Capture in Slow Ne7+–Helium Collisions.
- Author
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Fischer, D., Feuerstein, B., Moshammer, R., López-Urrutia, J. R. Crespo, Draganic, I., Lörch, H., Perumal, A. N., Ullrich, J., and DuBois, R. D.
- Subjects
ELECTRONS ,LEPTONS (Nuclear physics) ,CONSTITUTION of matter ,PARTICLES (Nuclear physics) ,SPECTRUM analysis ,NUCLEAR physics - Abstract
Single electron capture in collisions of 9 keV/q Ne
7+ -ions with He has been studied using cold-target recoil-ion momentum spectroscopy (COLTRIMS). With an improved apparatus a longitudinal momentum resolution of 0.07 a.u. has been achieved. This momentum component corresponds to the binding energy of the active electron in the final state. For the first time state-resolved differential cross sections have been determined with respect to the main quantum number, subshell level and spin state of the captured electron. [ABSTRACT FROM AUTHOR]- Published
- 2003
- Full Text
- View/download PDF
106. State-resolved measurements of single-electron capture in slow Ne7+- and Ne8+-helium collisions.
- Author
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Fischer, D, Feuerstein, B, DuBois, R D, Moshammer, R, L�pez-Urrutia, J R Crespo, Draganic, I, L�rch, H, Perumal, A N, and Ullrich, J
- Published
- 2002
- Full Text
- View/download PDF
107. Collection of MNCs with two cell separators for adoptive immunotherapy in patients with stage IV melanoma.
- Author
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Glaser, A., Schuler-Thurner, B., Feuerstein, B., Zingsera, J., Zimmermann, R., Weisbach, V., Eckstein, R., and Zingsem, J
- Subjects
MELANOMA treatment ,COLLECTION & preservation of biological specimens ,BLOOD platelets ,CELL separation ,CLINICAL trials ,COMPARATIVE studies ,COMPUTER software ,IMMUNIZATION ,RESEARCH methodology ,MEDICAL cooperation ,MELANOMA ,MONOCYTES ,RESEARCH ,TUMOR classification ,EVALUATION research ,CYTAPHERESIS - Abstract
Background: MNCs for adoptive immunotherapy may be collected by leukocytapheresis with a cell separator.Study Design and Methods: Six healthy cytapheresis donors donated two MNC concentrates on a cell separator (AS.TEC 204, Fresenius): one on the standard MNC program and one on a modified MNC program with reduced centrifuge velocity that leads to a lower platelet contamination. Seventeen patients with malignant melanoma donated 26 MNC concentrates: 5 on the AS.TEC 204 MNC program, 9 on the modified AS.TEC 204 MNC program, and 12 on another modified MNC program (Spectra, COBE).Results: In the course of cultivation of MNCs to dendritic cells (DCs), the donor MNC concentrates with the lower platelet contamination (475 +/- 85 x 10(9)/L) had a significantly higher relative DC yield (low platelet contamination: 3.9 +/- 1.6% of the plated cells; high platelet contamination: 2.5 +/- 1.8% of the plated cells; p = 0.019) than the concentrates with the higher platelet contamination (2364 +/- 448 x 10(9)/L). No significant difference was found in the yields of MNCs and CD14+ cells in the three protocols used for the collection of MNCs from patients with melanoma. The components obtained by the standard AS.TEC 204 MNC program had a significantly higher platelet contamination (1768 +/- 994 x 10(9)/L) than the components obtained by the modified AS.TEC MNC program (360 +/- 98 x 10(9)/L; p<0.05) and the modified Spectra MNC program (636 +/- 266 x 10(9)/L); p<0.05). Because of the low number of investigated components, no significant difference in the DC yield of the three protocols could be detected (mean DC yield after cultivation: 746 +/- 429 x 10(6)).Conclusion: A high platelet contamination of MNC concentrates intended for adoptive immunotherapy can lead to a significant impairment of the DC yield after cultivation. Both the modified AS.TEC 204 and the modified Spectra MNC programs are well suited for collecting MNC concentrates with high MNC yields and low platelet contamination from patients with malignant melanoma. [ABSTRACT FROM AUTHOR]- Published
- 2001
- Full Text
- View/download PDF
108. Cross sections of the 3p-1 diagram and satellite Auger states in atomic calcium for electron impact.
- Author
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Feuerstein, B, Zatsarinny, O I, and Mehlhorn, W
- Published
- 2000
- Full Text
- View/download PDF
109. Comparative genomic hybridization in patients with supratentorial and infratentorial primitive neuroectodermal tumors.
- Author
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Russo, Carolyn, Pellarin, Malgorzata, Tingby, Ola, Bollen, Andrew W., Lamborn, Kathleen R., Mohapatra, Gayatry, Collins, V. Peter, Feuerstein, Burt G., Russo, C, Pellarin, M, Tingby, O, Bollen, A W, Lamborn, K R, Mohapatra, G, Collins, V P, and Feuerstein, B G
- Published
- 1999
- Full Text
- View/download PDF
110. Time-resolved Imaging of H2+ (D2+) Nuclear Wave Packets.
- Author
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Castleman, A. W., Toennies, J. P., Zinth, W., Yamanouchi, K., Corkum, Paul, Jonas, David M., Miller, R. J. Dwayne., Weiner, Andrew M., Ergler, Th., Rudenko, A., Feuerstein, B., Zrost, K., Schröter, C. D., Moshammer, R., and Ullrich, J.
- Abstract
The spatio-temporal evolution of H2+ (D2+) nuclear wave packets is mapped using time-resolved Coulomb explosion imaging. We visualize the motion of both dissociating and bound parts of the wave packet, observe its dephasing and subsequent revivals. The reconstructed probability density of the wave packet is in good agreement with earlier theoretical predictions. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
111. Two polyamine analogs (BE-4-4-4 and BE-4-4-4-4) directly affect growth, survival, and cell cycle progression in two human brain tumor cell lines.
- Author
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Bergeron, Christophe, Basu, Hirak, Marton, Laurence, Deen, Dennis, Pellarin, Malgorzata, Feuerstein, Burt, Bergeron, C J, Basu, H S, Marton, L J, Deen, D F, Pellarin, M, and Feuerstein, B G
- Subjects
AMINES ,ANTINEOPLASTIC agents ,BRAIN tumors ,CHALONES ,COMPARATIVE studies ,FLOW cytometry ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,RESEARCH funding ,EVALUATION research ,CANCER cell culture ,PHARMACODYNAMICS - Abstract
1,14-Bis-(ethyl)-amino-5,10-diazatetradecane N1,N11-bis(ethyl)norspermine (BE-4-4-4) and 1,19-bis-(ethylamino)-5,10,15 triazanonadecane (BE-4-4-4-4) are two relatively new polyamine analogs synthesized for use as antineoplastic agents. In human brain tumor cell lines U-251 MG and SF-767, both agents inhibited cell growth, were cytotoxic, induced a variable G1/S block, and depleted intracellular polyamines. Since intracellular polyamine depletion did not always correlate with growth inhibition, cell survival, or cell cycle progression, it cannot completely explain the effects of these agents on growth, survival, and cell cycle progression in U-251 MG and SF-767 cells. [ABSTRACT FROM AUTHOR]
- Published
- 1995
- Full Text
- View/download PDF
112. Ultrafast mapping of H2+ (D2+) nuclear wave packets using time-resolved Coulomb explosion imaging
- Author
-
Ergler, Th, Rudenko, A, Feuerstein, B, Zrost, K, Schrter, C D, Moshammer, R, and Ullrich, J
- Abstract
The time evolution of H2+ (D2+) nuclear wave packets is studied exploiting a combination of coincident Coulomb explosion imaging and femtosecond pump–probe techniques. Using two 25 fs laser pulses, we map the motion of the dissociating molecular ion, observe an enhanced ionization rate at an internuclear separation of ∼11 au and resolve trajectories due to the one- and two-photon Floquet channels. With two 7 fs pulses, we are able to visualize the vibrational motion of the bound part of the wave packet, which exhibits counterintuitive quantum behaviour and dephases within about 100 fs, in agreement with recent numerical simulations.
- Published
- 2006
113. A method for the production of cryopreserved aliquots of antigen-preloaded, mature dendritic cells ready for clinical use
- Author
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Feuerstein, B., Berger, T. G., Maczek, C., Roder, C., Schreiner, D., Hirsch, U., Haendle, I., Leisgang, W., Glaser, A., and Kuss, O.
- Published
- 2000
- Full Text
- View/download PDF
114. Spermine-DNA interactions: a theoretical study.
- Author
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Feuerstein, B G, Pattabiraman, N, and Marton, L J
- Abstract
Models for the interaction of spermine and DNA were studied by performing conformational energy calculations on spermine and molecular mechanics calculations on major and minor groove complexes of spermine and oligomers of DNA. Docked into the major groove of B-DNA, spermine stabilizes the complex by maximizing interactions between proton acceptors on the oligomer and proton donors on spermine. This is achieved by bending the major groove of DNA over spermine and altering oligomer sugar puckering and interstrand phosphate distances. By comparison, Liquori's minor groove model appears to be less stable than the major groove model. This evidence favors a preferential binding of spermine to certain sites in DNA, which provides a powerful force for the modification of DNA conformation.
- Published
- 1986
- Full Text
- View/download PDF
115. Scrapie prions alter receptormediated calcium responses in cultured cells
- Author
-
Kristensson, K., Feuerstein, B., Taraboulos, A., Hyun, W. C., Prusiner, S. B., and DeArmond, S. J.
- Abstract
The molecular basis of neurologic dysfunction in prion diseases is unknown. Spongiform degeneration of neurons is the most characteristic neuropathologic change which raises the possibility of abnormal ion channel function. Here we examined the regulation of Ca2fluxes in two cell lines chronically infected with scrapie prions, designated ScN2a (scrapie-infected mouse neuroblatoma) and ScHaB (scrapie-infected hamster brain) cells. In uninfected HaB cells, bradykinin caused increases in iritracellular Ca2concentration ([Ca2]i) by release of Ca2from internal stores and influx of extracellular Ca2whereas, in N2a cells, bradykinin increased [Ca2]iexclusively from internal stores. Prion infection of both cell lines markedly reduced or eliminated bradykinin-activated increases in [Ca2]i, whether driven by internal or extracellular sources. Stressing the cells with high extracellular [Ca2], 8 to 20 mM, led to cytopathologic changes in ScHaB but not in ScN2a cells. Cytopathology was not preceded by an increase in [Ca2]i. These findings indicate that scrapie infection induces abnormalities in receptor-mediated Ca2responses and raise the possibility that nerve cell dysfunction and degeneration in prion diseases is related to ion channel aberrations.
- Published
- 1993
116. Diet and Exercise in Type 2 Diabetes Mellitus
- Author
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Feuerstein, B. L. and Weinstock, R. S.
- Published
- 1997
- Full Text
- View/download PDF
117. Gliomas in Families: Chromosomal Analysis by Comparative Genomic Hybridization
- Author
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Patel, A., Meyel, D. J. Van, Mohapatra, G., Bollen, A., Wrensch, M., Cairncross, J. G., and Feuerstein, B. G.
- Published
- 1998
- Full Text
- View/download PDF
118. Molecular dynamics of spermine-DNA interactions: sequence specificity and DNA bending for a simple ligand
- Author
-
Feuerstein, B G, Pattabiraman, N, and Marton, L J
- Subjects
Models, Molecular ,Binding Sites ,Base Sequence ,Molecular Conformation ,Nucleic Acid Conformation ,Computer Simulation ,Spermine ,DNA - Abstract
We used molecular dynamics to model interactions between the physiologically important polyamine spermine and two B-DNA oligomers, the homopolymer (dG)10-(dC)10 and the heteropolymer (dGdC)5-(dGdC)5. Water and counterions were included in the simulation. Starting coordinates for spermine-DNA complexes were structures obtained by molecular mechanics modeling of spermine with the two oligomers; in these models, spermine binding induced a bend in the heteropolymer but not in the homopolymer. During approximately 40 psec of molecular dynamics simulation, spermine moves away from the floor of the major groove and interacts nospecifically with d(G)10-d(C)10. In contrast, a spermine-induced bend in the helix of (dGdC)5-(dGdC)5 is maintained throughout the simulation and spermine remains closely associated with the major groove. These results provide further evidence that the binding of spermine to nucleic acids can be sequence specific and that bending of alternating purine-pyrimidine sequences may be a physiologically important result of spermine binding.
- Published
- 1989
119. Multiple ionization in strong fields
- Author
-
Artem Rudenko, Moshammer, R., Schröter, C. D., Zrost, K., Feuerstein, B., Jesus, V. L. B., and Ullrich, J.
- Subjects
Physics::Atomic and Molecular Clusters ,Physics::Atomic Physics - Abstract
Single and multiple ionization of rare gas atoms by 25 and 7 fs intense laser pulses has been studied using a "Reaction Microscope”. For single ionization of He, Ne and Ar in the tunnelling regime, surprising and distinct patterns have been observed in high-resolution low-energy electron spectra. Mechanisms of double and multiple ionization were elucidated and partly identified via recoil-ion momentum distributions and correlated electron spectra. For Ne the highly correlated “instantaneous” emission of up to four electrons is triggered by a recollisional electron impact, whereas in multiple ionization of Ar different mechanisms involving field ionization steps and recollision-induced excitations play a major role.
120. Physical chemistry 2007 | Physikalische Chemie 2007
- Author
-
Jochen Küpper, Meijer, G., Mews, A., Burghard, M., Ullrich, J. H., Feuerstein, B., and Wurth, W.
121. ChemInform Abstract: REACTIONS OF 1-(ACYLAMINO)-1,2,3,4-TETRAHYDROPYRIMIDINE-2-THIONES
- Author
-
HEYDENHAUSS, D., primary, JAENECKE, G., additional, and FEUERSTEIN, B., additional
- Published
- 1981
- Full Text
- View/download PDF
122. Recovery of adrenal function after failure resulting from traumatic bilateral adrenal hemorrhages.
- Author
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Feuerstein, Barbara, Strecten, David H.P., Feuerstein, B, and Streeten, D H
- Subjects
ADRENAL diseases ,TRAUMATISM ,ADRENOCORTICAL hormones ,HEMORRHAGE ,ADRENAL cortex ,ADRENAL glands ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,EVALUATION research ,ADRENAL insufficiency - Abstract
Presents a study which describes the complete recovery of adrenal function after severe adrenocortical insufficiency resulting from traumatic bilateral intra-adrenal hemorrhages. Overview of the case report; Results of the computer tomographic scans of the adrenal glands; Discussion.
- Published
- 1991
- Full Text
- View/download PDF
123. Intraoperative Discovery of Neuroblastoma in an Infant With Pulmonary Atresia
- Author
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McElhinney, D. B., Reddy, V. M., Feuerstein, B. G., Marx, G. R., and Hanley, F. L.
- Published
- 1997
- Full Text
- View/download PDF
124. Dennehy in a killer role.
- Author
-
Feuerstein, B.
- Subjects
- DENNEHY, Brian, 1938-2020
- Abstract
Reports that actor Brian Dennehy, who usually plays tough good guys, is starring as serial killer John Wayne Gacy in the two-part syndicated movie, `To Catch a Killer.' The film focuses on the investigation that led to Gacy's arrest.
- Published
- 1991
125. Electron-impact excitation cross sections of K*(3p54s2 2P3/2, 2P1/2) autoionizing states: strong fine-structure dependence near threshold.
- Author
-
Feuerstein, B., Grum-Grzhimailo, A. N., and Mehlhorn, W.
- Published
- 1999
- Full Text
- View/download PDF
126. Alignment of the Na* 2p53s2 2P3/2 autoionizing state excited by electron impact: experiment and theory.
- Author
-
Feuerstein, B., Grum-Grzhimailo, A. N., Bartschat, K., and Mehlhorn, W.
- Published
- 1999
- Full Text
- View/download PDF
127. Genetic gains and losses in neuroblastoma
- Author
-
Plantaz, D., Mohapatra, G., Matthey, K., Pellarin, M., Seeger, R., and Feuerstein, B. G.
- Published
- 1997
- Full Text
- View/download PDF
128. Geraldo is coming...
- Author
-
Feuerstein, B.
- Subjects
TELEVISION programs - Abstract
Announces that `Geraldo,' hosted by Geraldo Rivera, will soon become the first United States program and the first talk show ever scheduled on a daily basis on Soviet television.
- Published
- 1991
129. Targeting CD34+ cells of the inflamed synovial endothelium by guided nanoparticles for the treatment of rheumatoid arthritis
- Author
-
Jana Havrankova, Luis Nunez, Enrico Rampazzo, Enzo Terreno, Jakub Javurek, Romina Oliva, Costantino Pitzalis, Beatrice Belmonte, Claudio Tripodo, Stefania Biffi, Paola Bardini, Pier Luigi Meroni, Bernd Feuerstein, Gabriele Pozzato, Jessica Bertrand, Giada Maria Marini, Federico Colombo, Luca De Maso, Paolo Macor, Daniele Sblattero, Paolo Durigutto, Francesco Tedesco, Colombo, F., Durigutto, P., De Maso, L., Biffi, S., Belmonte, B., Tripodo, C., Oliva, R., Bardini, P., Marini, G. M., Terreno, E., Pozzato, G., Rampazzo, E., Bertrand, J., Feuerstein, B., Javurek, J., Havrankova, J., Pitzalis, C., Nunez, L., Meroni, P., Tedesco, F., Sblattero, D., Macor, P., Colombo F., Durigutto P., De Maso L., Biffi S., Belmonte B., Tripodo C., Oliva R., Bardini P., Marini G.M., Terreno E., Pozzato G., Rampazzo E., Bertrand J., Feuerstein B., Javurek J., Havrankova J., Pitzalis C., Nunez L., Meroni P., Tedesco F., Sblattero D., and Macor P.
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Biodistribution ,CD34 ,+ ,cells ,Neoangiogenesis ,Rheumatoid arthritis ,Targeted nanoparticles ,Targeted therapy ,medicine.medical_treatment ,Immunology ,Arthritis ,Inflammation ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Immunology and Allergy ,Progenitor cell ,Rheumatoid arthriti ,Targeted nanoparticle ,030203 arthritis & rheumatology ,business.industry ,cell ,medicine.disease ,Neoangiogenesi ,030104 developmental biology ,Toxicity ,Cancer research ,Methotrexate ,medicine.symptom ,business ,medicine.drug - Abstract
Despite the advances in the treatment of rheumatoid arthritis (RA) achieved in the last few years, several patients are diagnosed late, do not respond to or have to stop therapy because of inefficacy and/or toxicity, leaving still a huge unmet need. Tissue-specific strategies have the potential to address some of these issues. The aim of the study is the development of a safe nanotechnology approach for tissue-specific delivery of drugs and diagnostic probes. CD34 + endothelial precursors were addressed in inflamed synovium using targeted biodegradable nanoparticles (tBNPs). These nanostructures were made of poly-lactic acid, poly-caprolactone, and PEG and then coated with a synovial homing peptide. Immunofluorescence analysis clearly demonstrated their capacity to selectively address CD34 + endothelial cells in synovial tissue obtained from human, mouse, and rat. Biodistribution studies in two different animal models of rheumatoid arthritis (antigen-induced arthritis/AIA and collagen-induced arthritis/CIA) confirmed the selective accumulation in inflamed joints but also evidenced the capacity of tBNP to detect early phases of the disease and the preferential liver elimination. The therapeutic effect of methotrexate (MTX)-loaded tBNPs were studied in comparison with conventional MTX doses. MTX-loaded tBNPs prevented and treated CIA and AIA at a lower dose and reduced administration frequency than MTX. Moreover, MTX-loaded tBNP showed a novel mechanism of action, in which the particles target and kill CD34 + endothelial progenitors, preventing neo-angiogenesis and, consequently, synovial inflammation. tBNPs represent a stable and safe platform to develop highly-sensitive imaging and therapeutic approaches in RA targeting specifically synovial neo-angiogenesis to reduce local inflammation.
- Published
- 2019
130. US Fourth-Year Medical Students: Diabetes Knowledge and Confidence Dissonance.
- Author
-
Pitter D, Indelicato AM, Morley CP, Feuerstein B, and Weinstock RS
- Abstract
Introduction: Self-assessed confidence is not a reliable indicator of knowledge levels, as multiple studies have shown; however, it is often used as a measure of knowledge. The purpose of this study is to identify whether the confidence of graduating students in a US medical school to diagnose and treat diabetes is correlated with their diabetes-related knowledge., Methods: We developed a 38-question survey, targeting students' external experiences, knowledge, and confidence related to the diagnosis, treatment, and prevention of diabetes. The survey includes six self-reported confidence questions and 15 multiple choice-style questions, to test diabetes knowledge. The survey was administered electronically using REDCap to the graduating medical school class (n=176) at Upstate Medical University. We calculated mean knowledge scores and confidence scores were calculated. We used Pearson correlation and t tests to assess for correlations and differences in the collected data. We also reviewed diabetes content in the current curriculum., Results: The response rate was 38%. The mean confidence score was 19.97 out of 30 (SD=3.92) and the mean knowledge score was 9.63 out of 15 (SD=2.09). Total knowledge and confidence scores were not correlated. A positive correlation between confidence in prescribing/adjusting medications to treat patients with type 1 diabetes and knowledge levels was found ( R =.325, P =.007). Academic electives, external experiences with diabetes, and demographics did not correlate with knowledge and confidence differences., Conclusions: Students overestimated their ability to adequately manage people with diabetes. Better approaches are needed to prepare future physicians to diagnose and treat diabetes., (© 2024 by the Society of Teachers of Family Medicine.)
- Published
- 2024
- Full Text
- View/download PDF
131. Close Your Eyes and See: Stroke Sequelae versus Functional Neurological Disorder in a Physician.
- Author
-
Weil EJ, Keyserling H, Feuerstein B, and Murphy O
- Subjects
- Female, Humans, Middle Aged, Disease Progression, Pain, Stroke complications, Stroke diagnostic imaging, Physicians, Conversion Disorder
- Abstract
The first author is a left-handed, 51-year-old nephrologist who experienced a neurologic event. She underwent neurosurgery complicated by hemorrhage. Postoperatively, she developed persistent vertigo and unilateral tongue pain which persisted for over 5 years. Early neuroimaging revealed expected encephalomalacia but no neuroanatomical basis for her symptoms. A functional neurological disorder was suspected, and she was seen by several psychiatrists and psychotherapists. However, she suspected a neuroanatomical lesion would better explain her unrelenting symptoms. After seeing many neurologists, a neuroanatomical diagnosis was finally made. The theory and practice of medicine mandate that subjective complaint guides the modality and interpretation of objective evidence. The final neurologist knew where on neuroimaging to look because she was guided by the patient's complaints - vertigo and unilateral tongue pain. In this case, detailed scrutiny of neuroimaging by a neurologist, after encephalomalacia and gliosis were fully completed, gave a more accurate neuroanatomical diagnosis and a more realistic prognosis., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2023
- Full Text
- View/download PDF
132. Identifying drug allergies by means of exposure testing - the frequency and nature of hypersensitivity reactions.
- Author
-
Welponer T, Brandlmaier M, Feuerstein B, and Bauer JW
- Abstract
Competing Interests: The authors declare no conflict of interest.
- Published
- 2022
- Full Text
- View/download PDF
133. Targeting CD34 + cells of the inflamed synovial endothelium by guided nanoparticles for the treatment of rheumatoid arthritis.
- Author
-
Colombo F, Durigutto P, De Maso L, Biffi S, Belmonte B, Tripodo C, Oliva R, Bardini P, Marini GM, Terreno E, Pozzato G, Rampazzo E, Bertrand J, Feuerstein B, Javurek J, Havrankova J, Pitzalis C, Nuñez L, Meroni P, Tedesco F, Sblattero D, and Macor P
- Subjects
- Animals, Antigens, CD34 metabolism, Disease Models, Animal, Humans, Nanoparticles chemistry, Neovascularization, Pathologic, Polyesters chemistry, Rats, Rats, Wistar, Arthritis, Rheumatoid therapy, Endothelial Cells immunology, Inflammation therapy, Methotrexate therapeutic use, Nanoparticles therapeutic use, Synovial Membrane immunology, Synovial Membrane pathology
- Abstract
Despite the advances in the treatment of rheumatoid arthritis (RA) achieved in the last few years, several patients are diagnosed late, do not respond to or have to stop therapy because of inefficacy and/or toxicity, leaving still a huge unmet need. Tissue-specific strategies have the potential to address some of these issues. The aim of the study is the development of a safe nanotechnology approach for tissue-specific delivery of drugs and diagnostic probes. CD34
+ endothelial precursors were addressed in inflamed synovium using targeted biodegradable nanoparticles (tBNPs). These nanostructures were made of poly-lactic acid, poly-caprolactone, and PEG and then coated with a synovial homing peptide. Immunofluorescence analysis clearly demonstrated their capacity to selectively address CD34+ endothelial cells in synovial tissue obtained from human, mouse, and rat. Biodistribution studies in two different animal models of rheumatoid arthritis (antigen-induced arthritis/AIA and collagen-induced arthritis/CIA) confirmed the selective accumulation in inflamed joints but also evidenced the capacity of tBNP to detect early phases of the disease and the preferential liver elimination. The therapeutic effect of methotrexate (MTX)-loaded tBNPs were studied in comparison with conventional MTX doses. MTX-loaded tBNPs prevented and treated CIA and AIA at a lower dose and reduced administration frequency than MTX. Moreover, MTX-loaded tBNP showed a novel mechanism of action, in which the particles target and kill CD34+ endothelial progenitors, preventing neo-angiogenesis and, consequently, synovial inflammation. tBNPs represent a stable and safe platform to develop highly-sensitive imaging and therapeutic approaches in RA targeting specifically synovial neo-angiogenesis to reduce local inflammation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
134. Screw Track Osteolysis in the Cementless Total Knee Replacement Design.
- Author
-
Klutzny M, Singh G, Hameister R, Goldau G, Awiszus F, Feuerstein B, Stärke C, and Lohmann CH
- Subjects
- Aged, Aged, 80 and over, Arthroplasty, Replacement, Knee methods, Biocompatible Materials adverse effects, Bone Cements, Cementation, Equipment Failure Analysis, Female, Humans, Male, Middle Aged, Osteoarthritis, Knee pathology, Osteolysis etiology, Prosthesis Design, Prosthesis Failure, Tibia pathology, Titanium adverse effects, Arthroplasty, Replacement, Knee adverse effects, Bone Screws adverse effects, Knee Prosthesis adverse effects, Osteoarthritis, Knee surgery, Osteolysis pathology, Tibia surgery
- Abstract
Background: There is a paucity of reports on osteolysis associated with tibial screw fixation in cementless total knee arthroplasty (TKA), and the pathophysiology is not clear. This study aimed to describe the pathology related to screw track osteolysis around the tibia in cementless TKA., Methods: The study cohort comprised 100 revised cementless TKAs with tibial screw fixation. Screw track osteolysis and various screw angles were analyzed radiologically. Tissue samples from the joint capsule and the osteolytic cavity were investigated for metal/polyethylene wear. The type of tissue response was determined using immunohistochemistry. Retrieved tibial polyethylene inserts were analyzed for screw hole impression and mode of wear. Tissue metal content was measured by inductively coupled plasma optical emission spectrometry. Electrochemical reactions between the tibial tray and the cancellous screws were investigated., Results: Radiological analysis showed screw track osteolysis predominantly at the medial aspect of the tibial component, and the severity of osteolysis positively correlated with smaller medial proximal tibial screw angles. Osteolysis was associated with high titanium concentrations but not with polyethylene particles. An open circuit potential between the screw and the tibial base plate was measured. Necrosis, osteolytic cyst formation and macrophages, T and B cells, and dendritic cells were present., Conclusion: The present study highlights the risk for screw track osteolysis in cementless TKA with screw fixation. Our data collectively suggest that titanium wear may contribute to screw track osteolysis in the cementless TKA design. The contribution of screw angles is difficult to prove., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
135. The effects of cobalt and chromium ions on transforming growth factor-beta patterns and mineralization in human osteoblast-like MG63 and SaOs-2 cells.
- Author
-
Drynda S, Drynda A, Feuerstein B, Kekow J, Lohmann CH, and Bertrand J
- Subjects
- Alkaline Phosphatase metabolism, Cell Differentiation drug effects, Cell Line, Gene Expression Regulation drug effects, Humans, Ions, Osteoblasts drug effects, Osteoblasts metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Transforming Growth Factor beta genetics, Calcification, Physiologic drug effects, Chromium pharmacology, Cobalt pharmacology, Osteoblasts cytology, Transforming Growth Factor beta metabolism
- Abstract
Bone homeostasis, the balance of bone formation and resorption is affected by numerous influences, such as, hormones, inflammation, mechanical load, and external stimuli. The transforming growth factor-beta (TGF-β), which exists in three isoforms in humans, is a major factor in the maintenance of this balance by regulating osteoblast and osteoclast maturation, development, and function. In artificial joint replacements, release of particles or ions from arthroplasties may exert local effects on the periprosthetic tissue and modulate the expression of bone specific genes and functions. Therefore, the influence of cobalt (II) and chromium (III) ions on the expression levels of the three TGF-β isoforms in human osteosarcoma cell lines MG63 and SaOs-2 was analyzed and the impact on mineralization was studied. The osteosarcoma cell lines expressed all three TGF-β isoforms, with TGF-β1 being the most abundant isoform. A dose dependent reduction of all TGF-β isoforms by Co
2+ ions was observed, the strongest effect was found on TGF-β2. The effect was lesser pronounced in SaOs-2 cells. However, the Cr3+ ions had no significant effect on the expression of all TGF-β isoforms. In contrast, Co2+ ions in a concentration range of 50-250 µM did not impair the mineralization, but Cr3+ exerted a strong inhibitory effect on the mineralization in a dose dependent fashion. These data suggest that the influence of cobalt ions on bone homeostasis may in part result from the inhibitory effect on the transcription of the bone regulating cytokines TGF-β1-3 whereas the chromium ions affect the process of mineralization. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2105-2115, 2018., (© 2018 Wiley Periodicals, Inc.)- Published
- 2018
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136. Ballooning osteolysis in 71 failed total ankle arthroplasties.
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Singh G, Reichard T, Hameister R, Awiszus F, Schenk K, Feuerstein B, Roessner A, and Lohmann C
- Subjects
- Adult, Aged, Ankle Joint diagnostic imaging, Female, Follow-Up Studies, Germany epidemiology, Humans, Incidence, Male, Middle Aged, Osteolysis diagnosis, Osteolysis epidemiology, Prosthesis Design, Prosthesis Failure, Reoperation, Retrospective Studies, Tomography, Spiral Computed, Ankle Joint surgery, Arthroplasty, Replacement, Ankle adverse effects, Joint Prosthesis adverse effects, Osteoarthritis surgery, Osteolysis etiology
- Abstract
Background and purpose - Aseptic loosening is a major cause of failure in total ankle arthroplasty (TAA). In contrast to other total joint replacements, large periarticular cysts (ballooning osteolysis) have frequently been observed in this context. We investigated periprosthetic tissue responses in failed TAA, and performed an element analysis of retrieved tissues in failed TAA. Patients and methods - The study cohort consisted of 71 patients undergoing revision surgery for failed TAA, all with hydroxyapatite-coated implants. In addition, 5 patients undergoing primary TAA served as a control group. Radiologically, patients were classified into those with ballooning osteolysis and those without, according to defined criteria. Histomorphometric, immunohistochemical, and elemental analysis of tissues was performed. Von Kossa staining and digital microscopy was performed on all tissue samples. Results - Patients without ballooning osteolysis showed a generally higher expression of lymphocytes, and CD3+, CD11c+, CD20+, and CD68+ cells in a perivascular distribution, compared to diffuse expression. The odds of having ballooning osteolysis was 300 times higher in patients with calcium content >0.5 mg/g in periprosthetic tissue than in patients with calcium content ≤0.5 mg/g (p < 0.001). Interpretation - There have been very few studies investigating the pathomechanisms of failed TAA and the cause-effect nature of ballooning osteolysis in this context. Our data suggest that the hydroxyapatite coating of the implant may be a contributory factor.
- Published
- 2016
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137. Expression of CD11c in periprosthetic tissues from failed total hip arthroplasties.
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Chamaon K, Barber H, Awiszus F, Feuerstein B, and Lohmann CH
- Subjects
- Adult, Aged, Aged, 80 and over, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, Female, Humans, Immunohistochemistry, Lipopolysaccharide Receptors metabolism, Male, Metals adverse effects, Middle Aged, Prosthesis-Related Infections etiology, Arthroplasty, Replacement, Hip adverse effects, CD11c Antigen metabolism, Prosthesis Failure
- Abstract
In this work, we characterize integrin CD11c (αXß2) expression in periprosthetic tissues of 45 hip revisions. Tissues were retrieved from 23 ceramic-on-ultra-high molecular weight polyethylene (UHMWPE), 20 metal-on-UHMWPE, and 2 metal-on-metal total hip arthroplasties (THAs). Capsular tissue retrieved during primary THA from 19 patients served as controls. We identified a system to identify important immunohistochemical markers that are expressed in aseptic loosening. We focused on CD11c, CD68 and CD14. We observed that the CD11c molecule possesses four different cellular patterns in the periprosthetic tissues. Three of them are associated with the occurrence of UHMWPE abrasive material. Double staining with CD14 and CD68 was used for a more detailed analysis of the CD11c expressing cells. We observed that all forms of CD11c positive cells are CD68 positive however, only two forms of CD11c expressing cells are positive for CD14. Providing cellular diversity of CD11c expression in periprosthetic tissue, our results provide a contribution toward the further understanding of different cellular mechanisms to foreign body material., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2016
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138. Metallic wear debris may regulate CXCR4 expression in vitro and in vivo.
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Drynda A, Singh G, Buchhorn GH, Awiszus F, Ruetschi M, Feuerstein B, Kliche S, and Lohmann CH
- Subjects
- Aged, Alloys pharmacology, Blotting, Western, Cell Line, Cobalt pharmacology, Demography, Female, Gene Expression Regulation drug effects, Humans, Immunohistochemistry, Male, Metal-on-Metal Joint Prostheses adverse effects, Middle Aged, Osteoblasts metabolism, Receptors, CXCR4 genetics, Metals adverse effects, Prostheses and Implants adverse effects, Receptors, CXCR4 metabolism
- Abstract
CXCR4, the chemokine receptor for CXCL12, also known as SDF-1 (stromal cell derived factor-1), has been shown to play a pivotal role in bone metastasis, inflammatory, and autoimmune conditions but has not been investigated in periprosthetic osteolysis. We co-cultured osteoblast-like cells with increasing concentrations of metallic (Co-35Ni-20Cr-10Mo and Co-28Cr-6Mo) and Co-ions simulating wear debris. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to quantify gene and protein expression of CXCR4. The expression of tumor necrosis factor-alpha (TNF-α) and the effects of AMD3100 (bicyclam) on both CXCR4 and TNF-α expression among these cells was investigated. RT-PCR showed an increase in CXCR4 mRNA (7.5-fold for MG63 and 4.0-fold for SaOs-2 cells) among cells co-cultured with metal alloy particles. Western blotting showed a time-dependent increase in protein expression of CXCR4. The attempted blockade of CXCR4 by its known competitive receptor agonist AMD3100 led to a significant inhibition TNF-α mRNA expression. Immunohistochemistry showed CXCR4 positivity among patients with failed metal-on-metal hip replacements and radiographic evidence of osteolysis. Our data collectively suggest that the CXCR4 chemokine is upregulated in a dose- and time-dependent manner in the presence of metallic wear debris., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2015
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139. Low-frequency sonication may alter surface topography of endoprosthetic components and damage articular cartilage without eradicating biofilms completely.
- Author
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Singh G, Hameister R, Feuerstein B, Awiszus F, Meyer H, and Lohmann CH
- Subjects
- Bacterial Adhesion, Humans, Microbial Viability, Surface Properties, Biofilms, Chromium Alloys, Knee Prosthesis microbiology, Sound, Staphylococcus epidermidis physiology
- Abstract
Two-stage exchange arthroplasty is the current standard of care for arthroplasty-related infections. Reinfection rates up to 30% are reported, and there is significant morbidity for the patient. In cases of failure, arthrodesis or amputation may result. Ultrasonic treatment has the potential to eradicate biofilms and avoid two-stage exchange arthroplasty. Data in the specific context of arthroplasty infections is scant, and there is debate regarding optimal frequency and intensity of treatment. Surface topography alterations of the endoprosthetic components and damage to adjacent bone and cartilage have not been investigated. We found incomplete biofilm eradication and significant increase in surface roughness (maximum peak-to-valley height) of cobalt-chrome unicondylar knee components as well as reduction in articular cartilage thickness area from 10 retrieved femoral heads after low-frequency sonication treatment according to manufacturer-specified recommendations. Our data collectively suggest that sonication treatment for biofilm eradication in arthroplasty infections may not be effective and surface topography alterations may potentially reduce implant longevity., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
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140. Ceramic femoral component fracture in total knee arthroplasty: an analysis using fractography, fourier-transform infrared microscopy, contact radiography and histology.
- Author
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Krueger AP, Singh G, Beil FT, Feuerstein B, Ruether W, and Lohmann CH
- Subjects
- Biocompatible Materials, Ceramics, Female, Humans, Middle Aged, Arthroplasty, Replacement, Knee adverse effects, Equipment Failure Analysis methods, Knee Prosthesis adverse effects, Osteoarthritis, Knee surgery, Prosthesis Failure
- Abstract
Ceramic components in total knee arthroplasty (TKA) are evolving. We analyze the first case of BIOLOX delta ceramic femoral component fracture. A longitudinal midline fracture in the patellar groove was present, with an intact cement mantle and no bony defects. Fractographic analysis with laser scanning microscopy and white light interferometry showed no evidence of arrest lines, hackles, wake hackles, material flaws, fatigue or crack propagation. Analysis of periprosthetic tissues with Fourier-transform infrared (FT-IR) microscopy, contact radiography, histology, and subsequent digestion and high-speed centrifugation did not show ceramic debris. A macrophage-dominated response was present around polyethylene debris. We conclude that ceramic femoral component failure in this case was related to a traumatic event. Further research is needed to determine the suitability of ceramic components in TKA., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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141. Sulforhodamine 101 selectively labels human astrocytoma cells in an animal model of glioblastoma.
- Author
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Georges JF, Martirosyan NL, Eschbacher J, Nichols J, Tissot M, Preul MC, Feuerstein B, Anderson T, Spetzler RF, and Nakaji P
- Subjects
- Animals, Cell Line, Tumor, Coloring Agents, Humans, Male, Rats, Xenograft Model Antitumor Assays methods, Astrocytoma pathology, Brain Neoplasms diagnosis, Disease Models, Animal, Glioblastoma diagnosis, Rhodamines
- Abstract
Sulforhodamine 101 (SR101) is a useful tool for immediate staining of astrocytes. We hypothesized that if the selectivity of SR101was maintained in astrocytoma cells, it could prove useful for glioma research. Cultured astrocytoma cells and acute slices from orthotopic human glioma (n=9) and lymphoma (n=6) xenografts were incubated with SR101 and imaged with confocal microscopy. A subset of slices (n=18) were counter-immunostained with glial fibrillary acidic protein and CD20 for stereological assessment of SR101 co-localization. SR101 differentiated astrocytic tumor cells from lymphoma cells. In acute slices, SR101 labeled 86.50% (±1.86; p<0.0001) of astrocytoma cells and 2.19% (±0.47; p<0.0001) of lymphoma cells. SR101-labeled astrocytoma cells had a distinct morphology when compared with in vivo astrocytes. Immediate imaging of human astrocytoma cells in vitro and in ex vivo rodent xenograft tissue labeled with SR101 can identify astrocytic tumor cells and help visualize the tumor margin. These features are useful in studying astrocytoma in the laboratory and may have clinical applications., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2014
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142. Label-free microscopic assessment of glioblastoma biopsy specimens prior to biobanking [corrected].
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Georges J, Zehri A, Carlson E, Nichols J, Mooney MA, Martirosyan NL, Ghaffari L, Kalani MY, Eschbacher J, Feuerstein B, Anderson T, Preul MC, Van Keuren-Jensen K, and Nakaji P
- Subjects
- Animals, Biopsy, Cell Line, Tumor, Humans, Microscopy, Confocal methods, Rats, Rats, Nude, Xenograft Model Antitumor Assays methods, Biological Specimen Banks standards, Brain Neoplasms pathology, Glioblastoma pathology
- Abstract
Glioblastoma is the most common primary brain tumor with a median 12- to 15-month patient survival. Improving patient survival involves better understanding the biological mechanisms of glioblastoma tumorigenesis and seeking targeted molecular therapies. Central to furthering these advances is the collection and storage of surgical biopsies (biobanking) for research. This paper addresses an imaging modality, confocal reflectance microscopy (CRM), for safely screening glioblastoma biopsy samples prior to biobanking to increase the quality of tissue provided for research and clinical trials. These data indicate that CRM can immediately identify cellularity of tissue biopsies from animal models of glioblastoma. When screening fresh human biopsy samples, CRM can differentiate a cellular glioblastoma biopsy from a necrotic biopsy without altering DNA, RNA, or protein expression of sampled tissue. These data illustrate CRM's potential for rapidly and safely screening clinical biopsy samples prior to biobanking, which demonstrates its potential as an effective screening technique that can improve the quality of tissue biobanked for patients with glioblastoma.
- Published
- 2014
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143. Large-diameter metal-on-metal total hip arthroplasties: a page in orthopedic history?
- Author
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Singh G, Meyer H, Ruetschi M, Chamaon K, Feuerstein B, and Lohmann CH
- Subjects
- History, 20th Century, Humans, Ions, Prosthesis Failure, Arthroplasty, Replacement, Hip adverse effects, Metal-on-Metal Joint Prostheses adverse effects, Orthopedics history, Prosthesis Design
- Abstract
Large-diameter metal-on-metal (MoM) bearings evolved from the success of hip resurfacing. These implants were used in revision surgery in cases with well-fixed acetabular cups but loose or failed femoral stems, to avoid cup revision. Early data showed low rates of dislocation and potentially low wear profiles due to better fluid film lubrication. The risk of impingement was also thought to be low due to the increased head-neck ratio. Subsequently large-diameter MoM heads gained popularity in primary hip replacement. Recent data has emerged on the unacceptably high revision rates among patients with large-diameter MoM total hip arthroplasties (THAs), high blood levels of metal ions, and adverse tissue reactions. The head-neck (cone-taper) modular interface probably represents the weak link in large metal heads that have been used on conventional tapers. Increased torque of the large head, micromotion, and instability at the cone-taper interface, synergistic interactions between corrosion and wear, edge loading, low clearance, and psoas impingement are the likely causes for early failure of these prostheses., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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144. Correlations between perfusion MR imaging cerebral blood volume, microvessel quantification, and clinical outcome using stereotactic analysis in recurrent high-grade glioma.
- Author
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Hu LS, Eschbacher JM, Dueck AC, Heiserman JE, Liu S, Karis JP, Smith KA, Shapiro WR, Pinnaduwage DS, Coons SW, Nakaji P, Debbins J, Feuerstein BG, and Baxter LC
- Subjects
- Adult, Blood Volume Determination, Brain Neoplasms blood supply, Female, Humans, Male, Middle Aged, Neoplasm Recurrence, Local blood supply, Neoplasm Recurrence, Local prevention & control, Neovascularization, Pathologic pathology, Prognosis, Reproducibility of Results, Sensitivity and Specificity, Statistics as Topic, Stereotaxic Techniques, Treatment Outcome, Brain Neoplasms pathology, Brain Neoplasms surgery, Glioma pathology, Glioma surgery, Magnetic Resonance Angiography methods, Microvessels pathology, Neoplasm Recurrence, Local pathology
- Abstract
Background and Purpose: Quantifying MVA rather than MVD provides better correlation with survival in HGG. This is attributed to a specific "glomeruloid" vascular pattern, which is better characterized by vessel area than number. Despite its prognostic value, MVA quantification is laborious and clinically impractical. The DSC-MR imaging measure of rCBV offers the advantages of speed and convenience to overcome these limitations; however, clinical use of this technique depends on establishing accurate correlations between rCBV, MVA, and MVD, particularly in the setting of heterogeneous vascular size inherent to human HGG., Materials and Methods: We obtained preoperative 3T DSC-MR imaging in patients with HGG before stereotactic surgery. We histologically quantified MVA, MVD, and vascular size heterogeneity from CD34-stained 10-μm sections of stereotactic biopsies, and we coregistered biopsy locations with localized rCBV measurements. We statistically correlated rCBV, MVA, and MVD under conditions of high and low vascular-size heterogeneity and among tumor grades. We correlated all parameters with OS by using Cox regression., Results: We analyzed 38 biopsies from 24 subjects. rCBV correlated strongly with MVA (r = 0.83, P < .0001) but weakly with MVD (r = 0.32, P = .05), due to microvessel size heterogeneity. Among samples with more homogeneous vessel size, rCBV correlation with MVD improved (r = 0.56, P = .01). OS correlated with both rCBV (P = .02) and MVA (P = .01) but not with MVD (P = .17)., Conclusions: rCBV provides a reliable estimation of tumor MVA as a biomarker of glioma outcome. rCBV poorly estimates MVD in the presence of vessel size heterogeneity inherent to human HGG.
- Published
- 2012
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145. The Wnt inhibitory factor 1 (WIF1) is targeted in glioblastoma and has a tumor suppressing function potentially by induction of senescence.
- Author
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Lambiv WL, Vassallo I, Delorenzi M, Shay T, Diserens AC, Misra A, Feuerstein B, Murat A, Migliavacca E, Hamou MF, Sciuscio D, Burger R, Domany E, Stupp R, and Hegi ME
- Subjects
- Adaptor Proteins, Signal Transducing antagonists & inhibitors, Adaptor Proteins, Signal Transducing genetics, Animals, Blotting, Western, Brain Neoplasms genetics, Brain Neoplasms metabolism, Cell Adhesion, Cell Line, Tumor, Cell Proliferation, DNA Methylation, Down-Regulation, Epigenesis, Genetic, Female, Glioblastoma genetics, Glioblastoma metabolism, Humans, Immunoenzyme Techniques, Mice, Mice, Nude, Promoter Regions, Genetic, RNA, Messenger genetics, RNA, Small Interfering genetics, Repressor Proteins antagonists & inhibitors, Repressor Proteins genetics, Reverse Transcriptase Polymerase Chain Reaction, Adaptor Proteins, Signal Transducing metabolism, Aging, Brain Neoplasms prevention & control, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Glioblastoma prevention & control, Repressor Proteins metabolism
- Abstract
Gene expression-based prediction of genomic copy number aberrations in the chromosomal region 12q13 to 12q15 that is flanked by MDM2 and CDK4 identified Wnt inhibitory factor 1 (WIF1) as a candidate tumor suppressor gene in glioblastoma. WIF1 encodes a secreted Wnt antagonist and was strongly downregulated in most glioblastomas as compared with normal brain, implying deregulation of Wnt signaling, which is associated with cancer. WIF1 silencing was mediated by deletion (7/69, 10%) or epigenetic silencing by promoter hypermethylation (29/110, 26%). Co-amplification of MDM2 and CDK4 that is present in 10% of glioblastomas was associated in most cases with deletion of the whole genomic region enclosed, including the WIF1 locus. This interesting pathogenetic constellation targets the RB and p53 tumor suppressor pathways in tandem, while simultaneously activating oncogenic Wnt signaling. Ectopic expression of WIF1 in glioblastoma cell lines revealed a dose-dependent decrease of Wnt pathway activity. Furthermore, WIF1 expression inhibited cell proliferation in vitro, reduced anchorage-independent growth in soft agar, and completely abolished tumorigenicity in vivo. Interestingly, WIF1 overexpression in glioblastoma cells induced a senescence-like phenotype that was dose dependent. These results provide evidence that WIF1 has tumor suppressing properties. Downregulation of WIF1 in 75% of glioblastomas indicates frequent involvement of aberrant Wnt signaling and, hence, may render glioblastomas sensitive to inhibitors of Wnt signaling, potentially by diverting the tumor cells into a senescence-like state.
- Published
- 2011
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146. Steering the electron in H2(+) by nuclear wave packet dynamics.
- Author
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Fischer B, Kremer M, Pfeifer T, Feuerstein B, Sharma V, Thumm U, Schröter CD, Moshammer R, and Ullrich J
- Abstract
By combining carrier-envelope phase (CEP) stable light fields and the traditional method of optical pump-probe spectroscopy we study electron localization in dissociating H2(+) molecular ions. Localization and localizability of electrons is observed to strongly depend on the time delay between the two CEP-stable laser pulses with a characteristic periodicity corresponding to the oscillating molecular wave packet. Variation of the pump-probe delay time allows us to uncover the underlying physical mechanism for electron localization, which are two distinct sets of interfering dissociation channels that exhibit specific temporal signatures in their asymmetry response.
- Published
- 2010
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147. Optimized preload leakage-correction methods to improve the diagnostic accuracy of dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in posttreatment gliomas.
- Author
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Hu LS, Baxter LC, Pinnaduwage DS, Paine TL, Karis JP, Feuerstein BG, Schmainda KM, Dueck AC, Debbins J, Smith KA, Nakaji P, Eschbacher JM, Coons SW, and Heiserman JE
- Subjects
- Adult, Brain Neoplasms pathology, Female, Glioma pathology, Humans, Male, Middle Aged, Prospective Studies, Reproducibility of Results, Brain Neoplasms diagnosis, Brain Neoplasms surgery, Glioma diagnosis, Glioma surgery, Magnetic Resonance Angiography methods, Magnetic Resonance Angiography standards
- Abstract
Background and Purpose: Relative cerebral blood volume (rCBV) accuracy can vary substantially depending on the dynamic susceptibility-weighted contrast-enhanced (DSC) acquisition and postprocessing methods, due to blood-brain barrier disruption and resulting T1-weighted leakage and T2- and/or T2*-weighted imaging (T2/T2*WI) residual effects. We set out to determine optimal DSC conditions that address these errors and maximize rCBV accuracy in differentiating posttreatment radiation effect (PTRE) and tumor., Materials and Methods: We recruited patients with previously treated high-grade gliomas undergoing image-guided re-resection of recurrent contrast-enhancing MR imaging lesions. Thirty-six surgical tissue samples were collected from 11 subjects. Preoperative 3T DSC used 6 sequential evenly timed acquisitions, each by using a 0.05-mmol/kg gadodiamide bolus. Preload dosing (PLD) and baseline subtraction (BLS) techniques corrected T1-weighted leakage and T2/T2*WI residual effects, respectively. PLD amount and incubation time increased with each sequential acquisition. Corresponding tissue specimen stereotactic locations were coregistered to DSC to measure localized rCBV under varying PLD amounts, incubation times, and the presence of BLS. rCBV thresholds were determined to maximize test accuracy (average of sensitivity and specificity) in distinguishing tumor (n = 21) and PTRE (n = 15) samples under the varying conditions. Receiver operator characteristic (ROC) areas under the curve (AUCs) were statistically compared., Results: The protocol that combined PLD (0.1-mmol/kg amount, 6-minute incubation time) and BLS correction methods maximized test AUC (0.99) and accuracy (95.2%) compared with uncorrected rCBV AUC (0.85) and accuracy (81.0%) measured without PLD and BLS (P = .01)., Conclusions: Combining PLD and BLS correction methods for T1-weighted and T2/T2*WI errors, respectively, enables highly accurate differentiation of PTRE and tumor growth.
- Published
- 2010
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148. Electron localization in molecular fragmentation of H2 by carrier-envelope phase stabilized laser pulses.
- Author
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Kremer M, Fischer B, Feuerstein B, de Jesus VL, Sharma V, Hofrichter C, Rudenko A, Thumm U, Schröter CD, Moshammer R, and Ullrich J
- Abstract
Fully differential data for H2 dissociation in ultrashort (6 fs, 760 nm), linearly polarized, intense (0.44 PW/cm{2}) laser pulses with a stabilized carrier-envelope phase (CEP) were recorded with a reaction microscope. Depending on the CEP, the molecular orientation, and the kinetic energy release (KER), we find asymmetric proton emission at low KERs (0-3 eV), basically predicted by Roudnev and Esry, and much stronger than reported by Kling et al. Wave packet propagation calculations reproduce the salient features and discard, together with the observed KER-independent electron asymmetry, the first ionization step to be the reason for the asymmetric proton emission.
- Published
- 2009
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149. Relative cerebral blood volume values to differentiate high-grade glioma recurrence from posttreatment radiation effect: direct correlation between image-guided tissue histopathology and localized dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging measurements.
- Author
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Hu LS, Baxter LC, Smith KA, Feuerstein BG, Karis JP, Eschbacher JM, Coons SW, Nakaji P, Yeh RF, Debbins J, and Heiserman JE
- Subjects
- Biopsy, Blood Volume, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Combined Modality Therapy, Craniotomy, Diagnosis, Differential, Glioma radiotherapy, Glioma surgery, Humans, Magnetic Resonance Imaging standards, Neuronavigation, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity, Brain Neoplasms pathology, Cerebrovascular Circulation, Glioma pathology, Magnetic Resonance Imaging methods, Neoplasm Recurrence, Local pathology, Radiotherapy adverse effects
- Abstract
Background and Purpose: Differentiating tumor growth from posttreatment radiation effect (PTRE) remains a common problem in neuro-oncology practice. To our knowledge, useful threshold relative cerebral blood volume (rCBV) values that accurately distinguish the 2 entities do not exist. Our prospective study uses image-guided neuronavigation during surgical resection of MR imaging lesions to correlate directly specimen histopathology with localized dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC) measurements and to establish accurate rCBV threshold values, which differentiate PTRE from tumor recurrence., Materials and Methods: Preoperative 3T gradient-echo DSC and contrast-enhanced stereotactic T1-weighted images were obtained in patients with high-grade glioma (HGG) previously treated with multimodality therapy. Intraoperative neuronavigation documented the stereotactic location of multiple tissue specimens taken randomly from the periphery of enhancing MR imaging lesions. Coregistration of DSC and stereotactic images enabled calculation of localized rCBV within the previously recorded specimen locations. All tissue specimens were histopathologically categorized as tumor or PTRE and were correlated with corresponding rCBV values. All rCBV values were T1-weighted leakage-corrected with preload contrast-bolus administration and T2/T2*-weighted leakage-corrected with baseline subtraction integration., Results: Forty tissue specimens were collected from 13 subjects. The PTRE group (n = 16) rCBV values ranged from 0.21 to 0.71, tumor (n = 24) values ranged from 0.55 to 4.64, and 8.3% of tumor rCBV values fell within the PTRE group range. A threshold value of 0.71 optimized differentiation of the histopathologic groups with a sensitivity of 91.7% and a specificity of 100%., Conclusions: rCBV measurements obtained by using DSC and the protocol we have described can differentiate HGG recurrence from PTRE with a high degree of accuracy.
- Published
- 2009
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150. Spatiotemporal imaging of ultrafast molecular motion: collapse and revival of the D+2 nuclear wave packet.
- Author
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Ergler T, Rudenko A, Feuerstein B, Zrost K, Schröter CD, Moshammer R, and Ullrich J
- Abstract
We report on a real-time imaging of the ultrafast D(+)2 rovibrational nuclear wave-packet motion performed using a combination of a pump-probe setup with 7 fs laser pulses and a "reaction-microscope" spectrometer. We observe fast dephasing (collapse) of the vibrational wave packet and its subsequent revival and prove rotational excitation in ultrashort laser pulses. Channel-selective Fourier analysis of the wave packet's long-term (approximately 3000 fs) evolution allows us to resolve its individual constituents, revealing unique information on the mechanisms of strong-field ionization and dissociation.
- Published
- 2006
- Full Text
- View/download PDF
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